This invention relates to topical compositions of photoactivable agents and agents for absorbing or blocking extraneous radiation during phototherapy. The compositions are useful in methods for the treatment of various disorders such as psoriasis, CTCL, vertiligo, and other leukocyte mediated diseases.
A number of human diseases are mediated by certain types of leukocytes such as lymphocytes. Excessive or abnormal lymphocyte populations can result in numerous adverse effects to patients including the functional impairment of bodily organs, leukocyte mediated autoimmune diseases and leukemia related disorders. Some of these abnormal leukocyte mediated conditions can be alleviated effective using phototherapy in conjunction with psoralens. (See New England Journal of Medicine. 316:297 (1987); and Scientific American, August 1988, p. 68). The combination of psoralen ingestion or application together with UVA light to the skin is referred to as PUVA therapy. The psoralen is acts as a photosensitizer for the UVA treatment of the effected skin.
PUVA treatments involving the oral administration of 8-MOP followed by exposure to ultraviolet-A ( UVA light 320-400 nm wavelength) is often efficacious in the management of debilitating psoriasis vulgaris, a hyperproliferative disease of the epidermis. It has also been demonstrated that plaque stage cutaneous T cell lymphoma (CTCL), when limited to the skin, can respond favorably to this treatment (Gilchrest B. A., et al. Cancer (1976) 38: 683-689; Honigsmann H., et al. J. Am. Acad. Derm. (1984) 10:238-245).
There are several disadvantages with oral PUVA. In oral PUVA therapy, patients can experience nausea or find it difficult to achieve therapeutic levels of the psoralen. Additionally patients who can be treated with current oral dosages of methoxsalen may suffer from phototoxicity if they do not avoid sunlight or artificial sources of UVA light for 24 hours after receiving therapy. Other disadvantages include exposure of the affected skin area and the area surrounding the affected area with incidental UVB and or UVA radiation.
To avoid the systemic side effects of oral PUVA, topical PUVA treatments have been used in some cases. Psoralens such as 8 MOP tend to rapidly diffuse into and out of the skin making application to skin and treatment time thereafter difficult to manage. One approach to such PUVA treatment is the so-called “Bath PUVA” treatment in which the psoralen is essentially washed onto the patient in widespread fashion followed by broad UVA exposure. Bath PUVA has been used to treat dermatoses such as in lichen planus, systemic sclerosis and generalized morphoea, urticaria pigmentosa, mycosis fungoides, polymorphic light eruption, prurigo simplex subacuta, nodular prurigo, aquagenic pruritus, and lymphomatoid papulosis. See See Rhodes L. E. Guidelines for topical PUVA: a report of a workshop of the British Photodermatology Group, British Journal of Dermatology, 2000: 142: 22-31.
Other more locally applied topical psoralen formulations such as ointment, paint, aqueous gel, emulsion, lotion, and/or cream have also been used to treat dermatoses. These dermatoes include atopic dermatitis, lichen planus, systemic slerosis and generalized morphoea, vitiligo, uraemic pruitus, hyperkeratotic eczema, dyshidrotic eczema, hyperkeratotic psoriasis, and palmoplantar pustulosis. See Rhodes L. E. Guidelines for topical PUVA: a report of a workshop of the British Photodermatology Group, British Journal of Dermatology, 2000: 142: 22-31.
While topical PUVA treatments avoid the gastrointestinal and other systemic side-effects, topical PUVA treatments, as with oral and bath PUVA treatments, still suffer from the incidental exposure to UV radiation in the affected skin area and the surrounding skin area. For a PUVA treatment, commercially available high output UVA (320-400 nm) tube-style are utilized. However, these UVA radiation sources also emit some radiation in the 290-320 nm UVB region. Thus patients undergoing PUVA treatment are also exposed inadvertently to UVB radiation. Side effects include erythema, blistering and hyperpigmentation of the surrounding skin.
Psoralen formulations and method of treatments which allow a patient to undergo efficacioius PUVA treatments while minimizing exposure to incidental radiation in the affected area as well as in the area surrounding the affected area would be welcomed.
Current 8-MOP formulations, such as paints or ointments do not protect patients from UVB exposure and do not provide a means for protecting the area surrounding the affected area.
Despite the developments in psoralen compositions and methods of using them there remains a need for a psoralen formulation that is effective for phototherapy with UVA while protecting the affected area from residual UVB emitted by the irradiation source. The psoralen-based formulations provided in this specification comprise a UVB absorbing agent for providing such protection to the affected areas of the skin. The methods of the instant invention also alleviate undesirable incidental UVB and UVA radiation by administering to the area surrounding the affected area with a composition containing UVB and/or UVA absorbing agents.
The compositions of this invention comprise an oil phase having non-volatile compounds, photoactivable compounds such as a psoralen, and an UVB absorber. The oleaginous compositions of this invention contain a psoralen and an UVB absorbing agent in an essentially non-aqueous formulation.
The present invention also includes an improved PUVA method for treatment of diseases such as atopic dermatitis, lichen planus, systemic slerosis and generalized morphoea, vitiligo, uraemic pruitus, hyperkeratotic eczema, dyshidrotic eczema, hyperkeratotic psoriasis, and palmoplantar pustulosis. The affected skin areas are treated with UVA light and a pharmaceutically acceptable composition containing a psoralen and block out inadvertent UV radiation in the area surrounding the affected area with UVA and UVB absorbing agents.